Retrospective comparison between definitive stereotactic body radiotherapy and radical surgery for 538 patients with early-stage non-small cell lung cancer in a single institution.

Introduction: Survival information for stereotactic body radiotherapy (SBRT) and surgery for stage I non-small cell lung cancer (NSCLC) was examined. Methods: Stage I NSCLC patients who underwent surgery or SBRT between 2012 and 2016 were retrospectively enrolled in this single-institution study. Using the Kaplan--Meier method and Cox regression model, overall survival (OS) was estimated and compared. Results: Among 538 enrolled patients, compared to the surgery group (443), the SBRT group (95) had more complications (P = 0.01), worse performance status (P = 0.001), and were older (P < 0.001). Three-year OS was 70.5% post SBRT and 90.1% postsurgery. The 3-year cancer-specific survival (CSS) and disease-free survival (DFS) post SBRT and postsurgery were 92.7% vs. 92.3% and 61.1% vs 79.3%, respectively. Three-year locoregional and distant control rates post SBRT and postsurgery were 85.6% vs. 90.1% and 82.5% vs. 86.4%, respectively. Multivariate analysis using the Cox model, including age, T-stage, CCI, and C/T ratio and treatment, showed the surgery group's OS to be significantly superior to that of the SBRT group (HR of SBRT per surgery: 1.90, 95%CI: 1.12-3.21, P = 0.017). No significant differences were observed in rates of adverse events. Conclusion: Although OS was better in the surgery group, no differences in CSS existed. This analysis suggests the need for future studies that compare specific radical surgeries and SBRT in a prospective and randomized setting.

Dosimetric Comparison Study Between Free Breathing and Breath Hold Techniques in Patients Treated by Liver-Directed Stereotactic Body Radiation Therapy.

Background Breathing motion management is the key to delivering stereotactic body radiation therapy (SBRT) for liver lesions. This study aimed to compare the dosimetric parameters of liver SBRT using two different techniques: free breathing and breath hold. Method The study included 11 patients with liver metastases or hepatocellular carcinoma who underwent liver-directed SBRT. A dosimetric comparison was performed using dose-volume histogram analysis, evaluating parameters such as the maximum dose to 5 cc of bowel volume, mean liver dose (MLD), and liver V20 and V30. Statistical analyses were performed to compare results. Results The findings revealed that the breath hold technique resulted in significantly lower doses to the bowel and smaller volumes of normal liver tissue receiving 20 Gy (V20) and 30 Gy (V30) than the free breathing. Although there was no statistically significant difference in the MLD between the two techniques, the breath hold technique resulted in a lower MLD. Conclusion This dosimetric comparison study suggests that the breath hold technique is associated with lower radiation exposure to the bowel and normal liver tissues. Although this may not be feasible for all patients, it may be an appropriate procedure for selected individuals. Further research is needed to validate these findings in different patient populations and explore their impact on clinical outcomes and patient-reported quality of life.

Prognostic Factors for Patients With Brain Metastases Treated With Single-fraction Gamma Knife Radiosurgery.

BACKGROUND/AIM: The aim of this study was to identify prognostic factors for brain metastases treated with Gamma knife radiosurgery. PATIENTS AND METHODS: Multivariate Cox proportional hazards regression analyses were conducted for patients who received treatment between June 2013 and March 2018. RESULTS: A total of 131 consecutive patients were included. The median follow-up period was 16.0 months (range=1.5-61.5 months). Brain metastases [hazard ratio (HR)=0.42, 95%CI=0.27-0.67, p<0.001], history of systemic therapy (HR=2.23, 95%CI=1.28-3.89, p=0.005), and active extracranial disease (HR=2.49, 95%CI=1.30-4.76, p=0.006) were independent predictors of overall survival. Number of brain metastases (HR=0.39, 95%CI=0.26-0.59, p<0.001) and history of systemic therapy (HR=1.90, 95%CI=1.17-3.08, p=0.005) were independent predictors of intracranial progression-free survival. CONCLUSION: The number of brain metastases and the history of systemic therapy are associated with patient overall survival and intracranial progression-free survival.

Decreased miR122 in hepatocellular carcinoma leads to chemoresistance with increased arginine.

Reduced expression of microRNA122 (miR122), a liver-specific microRNA, is frequent in hepatocellular carcinoma (HCC). However, its biological significances remain poorly understood. Because deregulated amino acid levels in cancers can affect their biological behavior, we determined the amino acid levels in miR122-silenced mouse liver tissues, in which intracellular arginine levels were significantly increased. The increased intracellular arginine levels were through upregulation of the solute carrier family 7 (SLC7A1), a transporter of arginine and a direct target of miR122. Arginine is the substrate for nitric oxide (NO) synthetase, and intracellular NO levels were increased in miR122-silenced HCC cells, with increased resistance to sorafenib, a multikinase inhibitor. Conversely, maintenance of the miR122-silenced HCC cells in arginine-depleted culture media, as well as overexpression of miR122 in miR122-low-expressing HCC cells, reversed these effects and rendered the cells more sensitive to sorafenib. Using a reporter knock-in construct, chemical compounds were screened, and Wee1 kinase inhibitor was identified as upregulators of miR122 transcription, which increased the sensitivity of the cells to sorafenib. These results provide an insight into sorafenib resistance in miR122-low HCC, and suggest that arginine depletion or a combination of sorafenib with the identified compound may provide promising approaches to managing this HCC subset.